The British drug developer Domainex announced that the lead compound of their first-in-class small-molecule inhibitor has been shown to be more effective than either roflumulast or p38 inhibitors in a key model of chronic obstructive pulmonary disease (COPD). The inhibitors work by restraining two closely-related pro-inflammatory kinases TBK1 and IKK-epsilon (IKKɛ). The recent research has led the company to win a $2.4 million Biomedical Catalyst Award granted by the Technology Strategy Board to fund the company’s phase 1 clinical trials.
“These are very exciting results which suggest that our program could lead to an oral drug for the treatment of COPD with a much better anti-inflammatory effect than existing medicines,” said Dr. Trevor Perrior, the research director of Domainex, as quoted in a press release on Drug Discovery and Development. “This could provide the first truly-effective disease-modifying treatment for COPD, which would have an enormous impact on the management of this debilitating condition.”
The PDE4 inhibitor, roflumilast, and the p38 inhibitor are currently in late-stage clinical development, in which Domainex scientists are comparing the effects of the combined compounds with roflumilast or p38 administered separately in the same oral doses and analyzing it in a standard pre-clinical study COPD model. The results have shown that the combination more than doubles the effects in reducing the cigarette smoke-induced influx of inflammatory cells, particularly neutrophils, into the lung.
Inhibitors of TBK1 and IKKɛ had been proven to be potent anti-inflammatory agents in previous Domainex studies. The components disable the pathway signals activated by Toll-like Receptors and IL-17. The clinical trials suggest that the inhibitors are effective in the treatment of conditions such as rheumatoid arthritis, lupus, and psoriasis, however, the main recommendation derived from the study results is for the treatment of COPD, which is seen as a significant opportunity for the company.
“The disease is increasing in prevalence, particularly in certain countries, including China. It is estimated that the market is currently worth around $20bn. It is clear that an effective oral anti-inflammatory drug would not only achieve greater patient compliance, but would also treat the systemic inflammation which drives much of the morbidity and mortality caused by COPD, thereby addressing the major unmet medical need in this very important disease,” said Domainex’s CEO, Dr. Eddy Littler, noting that COPD is the fourth largest cause of death in the world and that over 70 million people are diagnosed with the disease.
Domainex also said they were grateful for the Technology Strategy Board who granted them the Biomedical Catalyst award, which they expect will enable the company to progress their COPD program to the Investigational New Drug stage. “In parallel with the company’s ongoing discussions with potential corporate partners, Domainex plans to seek funding to explore utility in other inflammatory diseases and take the program through to clinical proof of concept,” added the chairman, Keith Powell.